Separation of menthol from mint oils by chromatogrphic adsorption



United States Patent SEPARATION OF MEN THOL FROM MINT OILS BYCHROMATOGRAPHIC ABSORPTION Hson M. Chang, Kowloon, Hong Kong, assignorto Iowa State College Research Foundation, Inc., Ames, Iowa, acorporation of Iowa No Drawing. Application July 25, 1951, Serial No.238,570

1 Claim. (Cl. 260631) This invention relates to the separation ofmenthol from mint oils by' chromatographic adsorption. The invention isparticularly useful in the extraction of natural menthol from mint oilswith a very substantial increase in the yield of menthol over that ofexisting processes.

There are two general types of mint oils produced by the steamdistillation of the peppermint plants: Mentha piperita, grown mainly inthe United States and Europe, and Mentha arvensis, grown mainly inChina, Japan, and Brazil. The oil produced from Mentha piperita isgenerally known as peppermint oil, while the oil produced from Menthaarvensz's is usually designated as Chinese, Japanese, or Brazilian mintoil, according to its origin. The term mint oil will be used hereafterto include both types of oils containing a large amount of menthol.

Although the composition of mint oils is extremely complicated, thechief constituents may be classified as menthol, menthone, menthylesters, and terpene hydrocarbons. The oil from Mentha piperita usuallycontains 40 to 65% of menthol and 14 to 40% of menthone, while the oilfrom Mentha arvcnsis usually contains 60 to 85% of menthol and 12 to 20%menthone. Menthol and menthone are the two compounds present in all mintoils in large quantities and, due to their similar physical properties,the separation of these two compounds is the chief problem in theproduction of menthol from mint oils.

The traditionalmethod of producing menthol in China, Japan, and Brazilis to crystallize it from the mint oils at a temperature of about -l0 C.The method consists of three steps, namely, formation of mentholcrystals by freezing the natural mint oil, removal of the crystals fromthe residual oil by draining and centrifuging, and drying of thecrystals. Since menthol is very soluble in other constituents in mintoil even at low temperatures, a large portion of menthol is retained inthe residual oil. This so-called dementholized mint oil still containsabout 50% of menthol and is sold mostly to Europe as a cheap substitutefor peppermint oil at a price of about 25% of that of U. S.Pharmacopoeia grade menthol crystals. It is evident that by this method,the yield of menthol is low and drops rapidly for a small decrease ofthe original menthol content in the mint oil and only oil containingmore than 50% menthol can be used for the production of menthol. Thefree menthol content in American and European peppermint oil is usuallybelow 50% and therefore cannot be used as raw materials for theproduction of menthol by mere crystallization.

Some Brazilian manufacturers have tried to convert menthone in the mintoil into menthol by reduction, thereby increasing the yield of mentholfrom the enriched oil. While the natural menthol from the traditionalcrystallization process is laevo-active, the reduction of naturall-menthone in the mint oil yields, in addition to many undesirable sidereaction products, several isomers of menthol, the separation of whichis extremely difiicult and expensive. The price of synthetic racemicmenthol now on the market is only about two-thirds of that of naturall-menthol. Therefore, although the yield of menice thol after thereduction may be higher, the price of the isomeric product will beconsiderably lower, the over-all result may not be economical. Evidentlyit is better not to try the reduction process until menthol has beenseparated from the mint oil as much as possible. If menthone can also beisolated first and then reduced, it is much easier to control thereduction and higher yield of menthol may be expected.

Recently, efforts have been made at the Kitami factory in Japan toward amore complete recovery of menthol by first converting menthol into anon-volatile ester of boric acid, thus rendering the menthol readilyseparable from other volatile components. After removing the'volatilecomponents in the mint oil by steam distillation, the menthyl ester inthe residue is saponified with caustic alkali and the regeneratedmenthol is obtained by steam distillation again. Starting from anaverage mint oil containing of menthol, the yieldv by this process isillustrated as follows:

Yield 33% I menthone,. etc.)

Yield 23% Racemic menthol and isomenthol (non-crystallized) Yield 18%l-menthol-crystals Yield 12% By this method. the total yield ofl-menthol crystals increased from 40 to 52% of the natural mint oilbutdue to inversion in the process, part of the product could only beobtained as liquid isomeric menthol, the price of which should be evenlower than that of synthetic racemic menthol. The menthone oil containsabout 50% menthone, which is also racemized to a mixture of isomers, andis diflicult to market.

I have discovered that quantitative yields of both menthol and menthonecan be. obtained in a simpleprocess operable on a commercial basisthrough the use of adsorbents and selective eluants. In one embodimentof my invention, the mint oil is dissolved in a relatively nonpolarsolvent and then passed over an adsorbent, the adsorbed material thenbeing washed with eluants of increasing polarity to separate thementhone and menthol into clear-cut fractions. The pure menthol andmenthone may be then separated from the solvents by any desired means,as, for example, by evaporating the solvents.

The adsorbents may be those usually employed in chromatographic analysissuch as fullers earth, activated magnesia, activated charcoal, activatedalumina, etc.

The eluants are chosen with the object of obtaining rapid and completeliberation of one adsorbent at a time into clear-cut fractions.Non-polar solvents such as petroleum ether and carbon tetrachloride arepreferably used first to elute menthone without washing off menthol, andafter the complete elution of menthone, powerful eluants such asalcohols may be added to accelerate the elution of menthol in order tosecure a more concentrated solution.

I found that the components in the mint oil possess slightly diiferentadsorptive afiinities towards certain adsorbents. By the application ofthe chromatographic adsorption method I have discovered that menthol andmenthone can be obtained in substantially quantitative yields as purecompounds and no isomerization occurs during the process.

When a solution of the mint oil is adsorbed at the top of an adsorptioncolumn and then washed With properly selected solvents, the adsorbedsolutes are forced to migrate through the column. Under theseconditions, the weakly adsorbed components migrate rapidly and thestrongly adsorbed components migrate more slowly. As a result of thisdifferential migration, the adsorbed components gradually separate fromone another. The adsorption afiinity of the chief constituents of mintoils is in the following order: menthol, menthone, menthyl esters, andterpene hydrocarbons, the last being least adsorbed. Terpenehydrocarbons and menthyl esters are only very weakly adsorbed and can bewashed out readily by such weak eluants as petroleum ether. Menthol andmenthone have quite similar adsorptive properties, but if the adsorbentsand eluants are chosen judiciously, sharp separation of the two intoclear-cut fractions can be obtained under properly controlledconditions.

Both menthol and menthone obtained from the process are laevo-active andchemically unaltered. The menthol obtained from the process meets U. S.Pharmacopoeia specifications and no further purification is necessary.

As specific examples of the process, the following may be set out:

Example 1 A Chinese mint oil containing 65.2% menthol, 12.5%

menthone and 1.8% menthyl esters, was used as the raw material.Activated carbon (Carbide and Carbon Chemical Corporation, Columbiasolvent recovery grade) was ground and sieved to 100 or 200 mesh andused as adsorbent. A 6.5 cm. inside diameter glass column was packedwith 1200 grams of the aforesaid adsorbent to a height of approximately50 cm. Freshly steam-distilled mint oil in the amount of 25 grams wasdissolved in a hydrocarbon solvent with a boiling range of 77-l15 C.(Skellysolve D) to make up 150 ml. of solution and was adsorbed at thetop portion of the column. The column was then developed successivelywith 1000 ml. of a 80.20 by volume mixture of said hydrocarbon solvent(Skellysolve D):carbon tetrachloride, then with 600 ml. of pure carbontetrachloride, and finally with 700 ml. of 90: by volume mixture ofCClrzMeOH. The linear rate of flow of eluant was maintained at about 10mm./min. and the oil to adsorbent ratio was 1:50. 100 ml. fractions ofpercolate were collected and the solvents were evaporated. Threeclear-cut fractions were obtained: the terpenes and menthyl esters werewashed out first; the menthone fraction came out next; and the lastfraction contained only menthol. The melting point of the mentholfraction was within the U. S. P. specified range of 41 to 43 C. Thementhone fraction was nearly pure, as indicated by the refractive index.The yield of menthol and menthone were 95% and respectively. The lossesoccurred mainly during the evaporation of solvent.

Example 2 The process was carried out as described above, except thatpetroleum ether and carbontetrachloride were used first to elutementhone and thereafter alcohol was added to effect the elution ofmenthol.

Example 3 The process was carried out as described in Example 1, exceptthat the mint oil used as starting material was Mentha piperita.

In all of the examples set out above, the yields were considerably above90%, and When extreme care was used in the evaporation of the solvent,quantitative yields were obtained.

While in the foregoing specification, I have set forth specific steps inconsiderable detail for the purpose of illustrating embodiments of theinvention, it will be understood that such details of operation may bevaried widely by those skilled in the art without departing from thespirit of my invention.

I claim:

In a process for the separation of menthol from naturally-occurring mintoils, the steps of dissolving a naturally-occurring mint oil containingmenthol, menthone, menthyl esters and terpene hydrocarbons in apetroleum hydrocarbon solvent, passing the solution over an activeadsorbent for all of said mint oil constituents, Washing the adsorbentwhile said constituents are retained thereon with a petroleumhydrocarbon solvent to desorb the menthyl esters and terpenehydrocarbons, and then washing the adsorbent with a chlorinatedhydrocarbon solvent to desorb the menthone, and finally washing theadsorbent with an alcohol solvent to desorb the menthol.

References Cited in the file of this patent Strain: ChromatographicAdsorption Analysis, Interscience Publishers, Inc., New York, N. Y.(1945), pp. 90-92.

Vavon et al.: Comptes Rendus, vol. 226, pp. 1201- 1203 (1948).

Craw et al.: Univ. Queensland Papers, Dept. Chem., vol. 1, No. 31, 6pages (1948). Abstracted in Chemical Abstracts, vol. 44, p. 3945.

